Direct catalytic asymmetric aldol reaction

The direct catalytic asymmetric aldol reaction using aldehydes and unmodifi ed ketones is described for the first time herein. This reaction was first found to be promoted by 20 mol % of anhydrous (R)-LLB (L = lanthanum, L = l ithium, B = (R)-binaphthol moiety) at -20 OC, giving a variety of aldol pro ducts in ee's ranging from 44 to 94%. This asymmetric reaction has been gre atly improved by developing a new heteropolymetallic asymmetric catalyst [( R)-LLB, KOH, and H2O]. Using 3-8 mol % of this catalyst, a variety of direc t catalytic asymmetric aldol reactions were again found to proceed smoothly , affording aldol products in ee's ranging from 30 to 93% and in good to ex cellent yields. Interestingly, the use of this new heteropolymetallic asymm etric catalyst has realized a diastereoselective and enantioselective aldol reaction using cyclopentanone for the first time. It is also noteworthy th at a variety of aldehydes, including hexanal, can be utilized for the curre nt direct catalytic asymmetric aldol reaction. Chiral aldehydes containing alpha-hydrogen including (S)-hydrocinnamaldehyde-alpha-d have been found to produce the corresponding aldol products with negligible racemization (0-4 %) at the a-position One of the aldol products has been successfully conver ted to the key synthetic intermediates of epothilone A and bryostatin 7. Th e possible structure of the heteropolymetallic catalyst is also discussed. Finally, mechanistic studies have revealed a characteristic reaction pathwa y, namely that the reaction is kinetically controlled and the rate-determin ing step is the deprotonation of the ketone. This is consistent with the fa ct that the reaction rate is independent of the concentration of the aldehy de.